Prospective Investigation Research Articles

Pharmacokinetics of Sofosbuvir/Velpatasvir and efficacy of an alternate-day treatment in hemodialysis patients with chronic hepatitis C infection.

Sofosbuvir/Velpatasvir (SOF/VEL) is a combination drug used for chronic hepatitis C (HCV) infection. However, limited information exists regarding the pharmacokinetics of SOF/VEL and its metabolites in hemodialysis patients. We conducted a prospective investigation of the pharmacokinetic parameters of SOF/VEL after a single dose of SOF/VEL (400/100 mg) on days with and without dialysis in 12 Thai hemodialysis patients with chronic HCV infection, who had been undergoing hemodialysis for a duration of 0.5-20 years. Blood samples were collected before dose (0) and 0.5, 1.0, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, and 12.0 h after dose. Dialysate samples were also collected before dose (0) and 1.0, 2.0, 3.0, and 4.0 h after dose. Plasma and dialysate samples were quantified for SOF and its metabolite, GS-331007, and VEL concentrations using a fully validated LCMS technique. In addition, a preliminary efficacy study was conducted using the proposed SOF/VEL dose reduction regimen in all patients. No differences in SOF/VEL PK parameters between on- and off-dialysis studies. On the contrary, GS-331007 exhibited a 30% reduction in the area under the plasma concentration-time curve from time 0 to 24 h (AUC0-24h) on dialysis days compared with non-dialysis days (AUC0-24h ratio 0.68 vs. 1.04, respectively). The dialysis clearance of SOF and GS-331007 was 9.35 (8.72-15.11) and 8.89 (8.52-14.07) mL/min, respectively. Subsequently, an alternate-day regimen of SOF/VEL (400/100 mg) was administered for 12 weeks, resulting in an undetectable plasma HCV viral load without side effects. Further clinical studies are warranted to validate the efficacy and safety of our proposed dose reduction regimen.

Comparison of Dietary Patterns and Daily Food Intake Across Kidney Disease Stages in England: An A-Posteriori Cluster Analysis

ObjectiveDietary patterns are rapidly becoming a major focus of medical nutrition therapy in CKD and the analysis of dietary patterns has emerged as a practical approach to evaluate qualitative as well as quantitative aspects of overall diet. In an a-posteriori data-driven approach, dietary patterns are based on the actual food intake of the population evaluated. Investigation of dietary patterns in CKD are not well described, and, to our knowledge, have not been conducted in a UK-based cohort. MethodsAdult participants with a diagnosed kidney condition (CKD 1-5 not requiring dialysis) were recruited into a multi-centre observational cross-sectional study. Dietary intake was assessed using the European Prospective Investigation of Cancer in Norfolk Food Frequency Questionnaire. Logistic Principal Components Analysis was used to identify food group clusters. Differences between groups were assessed using univariate general linear modelling. ResultsIn total, 696 patients were included. The mean age was 64.7 (±14.0) years, 61% of the cohort were male. Most participants were White British (89%). The mean eGFR was 36.6 (±20.9) ml/min/1.732. We found differences in food group intake across stages (e.g., greater intake of nuts and seeds intake in CKD 1-2 versus CKD 4) and across sex (e.g., females had a higher intake of fruit and vegetables versus males). Comparison with the reference cohort revealed that, overall, the CKD cohort had reduced intakes of food stuffs such as cereals and cereal products, but higher intakes of groups such as meat and meat products. There were limited differences in micronutrients, although Vitamin B2 and calcium were higher in earlier stages. ConclusionOverall, the findings from a novel a-posteriori approach underline the complex diversity of food patterns in CKD. The findings from our study may inform dieticians and other healthcare providers about the need to consider treatment modalities and stages when giving dietary recommendations.

Immediate Weightbearing after Modified Lapidus Arthrodesis Using a Medial Plate: A Retrospective Descriptive Cohort Study

The modified Lapidus procedure has emerged as a versatile solution for various pedal pathologies, particularly hallux abducto valgus. There have been numerous modifications over time regarding fixation techniques, joint preparation methods, graft utilization, and weightbearing protocols. However, concerns persist regarding prolonged nonweightbearing postoperatively, prompting the need for alternative approaches. This retrospective descriptive cohort analysis assessed the outcomes of 40 feet from 34 patients who underwent the modified Lapidus procedure with a medial plating system, aimed to evaluate immediate weightbearing outcomes on union rate, fixation-related complications, and functional outcomes. Among the 40 feet, findings showed a 95% (38/40) union rate within 6 months, with 2.5% (1/40) experiencing delayed union and 2.5% (1/40) facing fixation-related complications. There is a single case of malunion in the cohort. Additionally, statistically significant improvements were observed across all domains of the Manchester-Oxford Foot Questionnaire at p < .001. These findings suggest immediate weightbearing as a potential alternative to traditional nonweightbearing protocols. However, the study's retrospective nature and lack of a comparative group warrant cautious interpretation. Further research is essential to validate these findings and refine postoperative care protocols. By challenging conventional practices, this study underscores the complexity of optimizing patient outcomes in modified Lapidus procedure management. Tailored approaches and prospective investigations are imperative for establishing definitive guidelines and enhancing surgical techniques in this domain.

The association between olfactory subdomains and frailty: A prospective case‒control study investigation.

Amidst the rise of frailty among a globally aging population, olfactory decline has emerged as a harbinger of frailty and mortality in population-level studies. However, the relationships between frailty and the olfactory subdomains of identification (OI), discrimination (OD), and threshold (OT) remain unexplored. This study prospectively examined the association between olfactory subdomains and the physical frailty phenotype (PFP) to investigate olfactory evaluation as a means of frailty screening. A case‒control study of 45 frail and 45 non-frail individuals matched by age and sex. OT, OD, OI (range 0‒16), and composite sum (threshold, discrimination, and identification scores [TDI], range 0‒48) were measured with Sniffin' Sticks. PFP was defined by presence of three or more criteria: physical inactivity, self-reported exhaustion, muscle weakness, slow gait, and unintentional weight loss. Conditional logistic regression evaluated associations between olfactory subdomains and frailty. Ninety individuals with mean age of 83.1±4.9 years, 60% female (n=54), and 87.8% white (n=79) were included. Olfactory scores were significantly lower in the frail group for OI (9.2vs. 12.1, p<0.001), OD (8.1vs. 11.6, p<0.001), OT (4.4vs. 8.5, p<0.001), and TDI (21.7vs. 32.2, p<0.001) than in the non-frail group. A single-point decrease in olfactory score was associated with increased odds of frailty in OT (odds ratio [OR]: 2.21, 95% confidence interval: [1.22, 3.98]), OD (OR: 2.19, 95% CI: [1.32, 3.65]), OI (OR: 2.29, 95% CI: [1.19, 4.39]), and TDI (OR: 1.54, 95% CI: [1.14, 2.08]). The robust association between olfactory subdomain scores and frailty suggests that olfaction may be an accessible signifier of frailty. Future studies should investigate this relationship longitudinally to assess predictive relationships.

Assembly and Comparative Analysis of the Complete Mitochondrial Genome of Ilex rotunda Thunb.

Ilex rotunda Thunb. stands as a representative tree species in subtropical evergreen broad-leaved forests, widely distributed across southeast Asia. This species holds significant value in forestry due to its ecological resilience and adaptability. Although researchers have conducted in-depth research on the plastid genome (plastome) of I. rotunda, the mitochondrial genome (mitogenome) of this species has remained undocumented. In the present study, we successfully sequenced and assembled the I. rotunda mitogenome. The mitogenome has a circular structure and is 567,552 bp in total length, with a GC content of 45.47%. The composition of the mitogenome encompasses 40 protein-coding genes, along with 3 rRNA genes and 19 tRNA genes. Notably, the mitogenome exhibits a universal distribution of repetitive sequences, but the total length of repeats contributes to a relatively small proportion (4%) of the whole mitogenome, suggesting that repeats do not serve as the primary cause of the amplification of the Ilex mitogenomes. Collinear analysis indicates that the I. rotunda mitogenome is very conservative within Aquifoliales species. Additionally, our research identified 51 fragments of plastid genomic DNA, which have migrated from the plastome into the mitogenome, with five genes from the plastome remaining intact. Eventually, the phylogenetic analyses based on the plastomes and mitogenomes of 36 angiosperms determine the Aquifoliales to be the basal group in the campanulids. This study establishes the bedrock for prospective investigations in molecular breeding research.

Perspective article: determinants and assessment of cardiovascular risk in steatotic liver disease owing to metabolic dysfunction-addressing the challenge

Metabolic dysfunction-associated steatotic liver disease (MASLD) stands as an independent risk factor for cardiovascular disease (CVD), which is the leading cause of mortality among MASLD patients. The diverse spectrum of cardio-nephro-metabolic and vascular manifestations inherent in MASLD highlights the complex profile of CVD risk associated with this condition. However, current approaches to assessing CVD risk in MASLD lack specificity, predominantly relying on traditional markers. Although it is widely accepted that patients with advanced fibrosis are more prone to CVD risk, recent evidence suggests that this isolated focus may overlook the remarkable phenotypic variability of this CVD risk across the entire MASLD population. Emerging data indicate a progressive escalation of CVD risk in parallel with the severity of MASLD, highlighting the need for precise disease staging to inform accurate risk assessment. To address this challenge, we propose a novel sequential approach to CVD risk assessment in MASLD. While traditional CVD risk factors remain essential, incorporating liver-specific parameters enhances risk stratification and guides targeted interventions to mitigate the substantial burden of cardiovascular disease in this vulnerable population. This approach involves initial screening using FIB-4 and NAFLD fibrosis score, followed by assessment of liver fibrosis with imaging-based non-invasive techniques in individuals at intermediate-high risk for advanced fibrosis and liver fat quantification in low-risk individuals. Future prospective investigations should focus on the simultaneous use of liver biomarkers and imaging modalities to evaluate, in a sex-specific manner, the efficacy of the proposed approach and to determine optimal thresholds of liver fibrosis and steatosis for optimal CVD risk assessment.

Stereotactic body radiotherapy is an alternative to radiofrequency ablation for single HCC ≤5.0 cm

Background & AimsRadiation therapy has been refined with the increasing evidence of stereotactic body radiation therapy (SBRT) in treating hepatocellular carcinoma (HCC). In this study, we aimed to evaluate whether SBRT could serve as an alternative to radiofrequency ablation (RFA) for small HCC with a single lesion ≤ 5.0 cm. MethodsPatients with a single HCC lesion ≤ 5.0 cm who received RFA or SBRT were included. Cumulative local/distant recurrence rate (CLRR/CDRR), progression-free survival (PFS), overall survival (OS), adverse events (AEs) and subsequent treatments after recurrence were analyzed. ResultsA total of 288 patients received RFA (166) or SBRT (122) were enrolled. The baseline characteristics between the two groups were comparable. The CLRR in the SBRT group was significantly lower than that in the RFA group (HR = 0.30, 95%CI = 0.16 – 0.57, P < 0.001), especially for patients with tumors > 2.0 cm (HR = 0.20, 95% CI = 0.08 – 0.50, P < 0.001) or adjacent to major vessels (HR = 0.29, 95% CI = 0.13 – 0.66, P < 0.001). CDRR, PFS and OS showed no significant differences between the two groups (all P > 0.050). AEs were mild and easily reversible. However, more patients in the SBRT group suffered from Child-Pugh score and TB increase. More treatment options after recurrence or progression might be available for patients in the RFA group compared to those in the SBRT group (P < 0.001). ConclusionsBoth RFA and SBRT were effective and safe for HCC with a single lesion ≤ 5.0 cm. SBRT could be an alternative treatment to RFA, especially for tumors > 2.0 cm or adjacent to major vessels. Impact and implicationsStereotactic body radiation therapy (SBRT) may be used as an alternative therapy to thermal ablation for patients with BCLC stage A hepatocellular carcinoma (HCC) who are not candidates for surgical resection, including those with tumors > 3 cm and those with 1 to 3 tumors. This study focused on HCC patients with specific tumor burden, a single lesion ≤ 5.0 cm, demonstrating that SBRT could be an effective and safe alternative to radiofrequency ablation (RFA), especially for those with tumors > 2.0 cm or adjacent to major vessels. The findings of this study provided robust empirical evidence supporting for the utilization of SBRT in treating small HCC, while also establishing a solid foundation for future prospective clinical investigations.

The maternal drug exposure birth cohort (DEBC) in China

Drug exposure during pregnancy lacks global fetal safety data. The maternal drug exposure birth cohort (DEBC) study, a prospective longitudinal investigation, aims to explore the correlation of maternal drug exposure during pregnancy with pregnancy outcomes, and establish a human biospecimen biobank. Here we describe the process of establishing DEBC and show that the drug exposure rate in the first trimester of pregnant women in DEBC (n = 112,986) is 30.70%. Among the drugs used, dydrogesterone and progesterone have the highest exposure rates, which are 11.97% and 10.82%, respectively. The overall incidence of adverse pregnancy outcomes is 13.49%. Dydrogesterone exposure during the first trimester is correlated with higher incidences of stillbirth, preterm birth, low birth weight, and birth defects, along with a lower incidence of miscarriage/abortion. Due to the limitations of this cohort study, causative conclusions cannot be drawn. Further follow-up and in-depth data analysis are planned for future studies.

Behavioral and cortical dynamics underlying superior accuracy in short-distance passes

Improved pass accuracy is a prominent determinant of success in football. It demands an effective interaction of complex behavioral and cortical dynamics. Exploring differences in the ability to sustain an accurate pass behavior in a stable setting and the associated cortical dynamics at different expertise levels may provide an insight into skilled strategies contributing to superior accuracy in football. The aim of this study is to compare trial-to-trial variability of pass biomechanics and the corresponding cortical dynamics during short-distance passes between novices and experienced football players. Thirty participants (15 novices, 15 football players) performed 90 short-distance passes. The intertrial variability of pass biomechanics (foot acceleration, range of hip flexion, knee flexion and foot rotation) was assessed by means of multiscale entropy. The task-related cortical dynamics were analyzed via source-derived event-related spectral perturbations. Experienced players demonstrated higher accuracy and overall lower entropy values across multiple time scales which was significant for hip flexion. The electroencephalography data revealed group differences in parieto-occipital alpha desynchronization and frontal theta synchronization in successive phases of passes. The current findings suggest that experienced football players may show a skilled ability to recruit and retain pass biomechanics promoting higher accuracy, whereas novices may show an explorative behavior with higher spatial variability. This difference may be associated with distinctive visuospatial and attentional strategies acquired with expertise in football. Our study provides an insight into expertise-specific behavioral and cortical dynamics of superior accuracy in football and a basis for its prospective investigation in enriched contexts.

Relationship of urinary glyphosate concentrations with glycosylated hemoglobin and diabetes in US adults: a cross-sectional study

BackgroundGlyphosate is a commonly used herbicide worldwide and is purportedly associated with multiple health effects. Research assessing the association of glyphosate concentrations with glycosylated hemoglobin (HbA1c) levels and the prevalence of diabetes is scarce. We sought to evaluate the association between urinary glyphosate levels and HbA1c levels and the prevalence of diabetes.MethodsA total of 2,745 adults in the National Health and Nutrition Examination Survey from 2013 to 2016 were included in this study. Generalized linear models (GLM) were applied to evaluate the associations of glyphosate concentrations with HbA1c levels and the prevalence of diabetes. The dose–response relationship was examined using restricted cubic splines (RCS).ResultsSignificantly positive correlations of urinary glyphosate concentrations with HbA1c levels (percentage change: 1.45; 95% CI: 0.95, 1.96; P < 0.001) and the prevalence of diabetes (OR: 1.45; 95% CI: 1.24, 1.68; P < 0.001) were found after adjustment. Compared with the lowest quartile of glyphosate levels, the highest quartile was positively associated with HbA1c levels (percentage change: 4.19; 95% CI: 2.54, 5.85; P < 0.001) and the prevalence of diabetes (OR: 1.89; 95% CI: 1.37, 2.63; P < 0.001). The RCS curves demonstrated a monotonically increasing dose–response relationship between urinary glyphosate levels and the prevalence of diabetes and HbA1c levels.ConclusionsUrinary glyphosate concentrations are positively associated with HBA1c levels and the prevalence of diabetes. To verify our findings, additional large-scale prospective investigations are required.

Advances in in-situ resources utilization for extraterrestrial construction

To establish foundational support for forthcoming deep space exploration and settlement endeavors, the significance of extraterrestrial construction has become paramount. Recent developments underscore a growing acknowledgment of the imperative role played by in situ resource utilization, attributed to its potential for cost efficiency and facilitation of sustainable progress. This paper compiles and categorizes the advancements in this domain, focusing on three distinctive categories of in situ resources: regolith, water–ice, and energy resources. A review of their distribution, acquisition, and utilization procedures is presented. Subsequently, an intricate examination ensues, elucidating the applicability of each resource within the context of extraterrestrial construction, in conjunction with five prevalent technologies and the latest architectural constructs. Drawing insights from the research, the existing limitations are identified, particularly pertaining to the comprehensive, deep processing, and sustainable utilization of resources. Consequently, a proposition is put forth to address these challenges. Prospective investigations are recommended, focusing on the mining of water–ice, the metallurgy and production of regolith and slag, and the integrated construction in the pursuit of extraterrestrial construction and operational endeavors.

Distribution of genetic polymorphism of the PTP1B gene in diabetes mellitus patients taking insulin therapy in Indonesia: A narrative review

Background: Diabetes mellitus is a metabolic disease directly related to the onset of hyperglycemia, which occurs due to abnormalities in insulin secretion, insulin action, or both. Protein Tyrosine Phosphatase 1B (PTP1B) from insulin receptor signal transduction has a role in the pathogenesis of diabetes mellitus. Objective: To briefly present the distribution of genetic polymorphism of the PTP1B gene in diabetes mellitus patients taking insulin therapy. Method: A narrative review was conducted by collecting scientific journals in English from several leading platforms, such as PubMed, CrossRef, and Google Scholar, published from 2012 to 2023. Result: PTP1B can inhibit glucose transporter type 4 (GLUT4) activation in glucose uptake by cells, increasing glucose levels. The use of exogenous insulin becomes ineffective, and insulin resistance occurs. This study has limitations and needs additional prospective investigations to corroborate the findings. Conclusion: In some studies, PTP1B gene polymorphism in diabetes mellitus patients strongly correlates with insulin therapy. PTP1B gene polymorphism can cause insulin resistance because PTP1B and GLUT4 have the opposite effect.

Molecular epidemiology, antibiotic resistance profile and frequency of integron 1 and 2 in adherent-invasive Escherichia coli isolates of colorectal cancer patients

This study explores the prevalence of adherent-invasive Escherichia coli (AIEC) in colorectal cancer (CRC) patients and investigates the potential of effective intracellular antibiotics as a therapeutic strategy for CRC patients with AIEC infections. Considering the pivotal role of integrons in bacterial antibiotic resistance, the frequency of class 1 and 2 integrons in AIEC isolated from CRC patients, in one of the referenced 3 gastroenterology clinics in Isfahan, Iran was examined. AIEC strains were isolated from the colorectal biopsies and their antimicrobial sensitivity was assessed using the disc diffusion method. Polymerase chain reaction (PCR) was employed to detect intl1 and intl2. The multilocus sequence typing (MLST) method was utilized to type 10 selected isolates. Of the 150 samples, 24 were identified as AIEC, with the highest number isolated from CRC2 (33.4%) and CRC1 (29.16%), and the least from the FH group (8.3%) and control group (12.5%). int1 in 79.2% and int2 in 45.8% of AIEC strains were found and 41.6% of strains had both integrons. AIEC isolates with int1 exhibited the highest sensitivity to trimethoprim-sulfamethoxazole (57.9%), while those with int2 showed the highest sensitivity to ciprofloxacin (63.6%). A significant association between resistance to rifampin and integron 2 presence in AIEC isolates was observed. Furthermore, a significant correlation between integron 1 presence, invasion, survival, and replication within macrophages in AIEC strains was identified. MLST analysis revealed ST131 from CC131 with integron 1 as the most common sequence type (ST). The emergence of such strains in CRC populations poses a serious public health threat. The distribution pattern of STs varied among studied groups, with pandemic STs highlighting the importance of examining and treating patients infected with these isolates. Comprehensive prospective clinical investigations are warranted to assess the prognostic value of detecting this pathovar in CRC and to evaluate therapeutic techniques targeting drug-resistant AIECs, such as phage therapy, bacteriocins, and anti-adhesion compounds, for CRC prevention and treatment.

Increased risk of atrial fibrillation with low cardiovascular health: life essential 8 in a dutch population

Abstract Introduction The American Heart Association (AHA) introduced the concept of Life’s Essential 8 (LE8) to measure and monitor cardiovascular health (CVH) to prevent cardiovascular diseases. Purpose This study examined the association between LE8 and the incidence of atrial fibrillation (AF). Methods In total, 37,807 participants from the population-based European Prospective Investigation Into Cancer and Nutrition-Netherlands (EPIC-NL) cohort were included. The components diet, physical activity, sleep health, nicotine exposure, body mass index, blood glucose, blood lipids, blood pressure were all given a score between 0 and 100 and an overall LE8 score was created by averaging the component scores. The overall LE8 score was categorized into low cardiovascular health (CVH, 0-49), moderate CVH (50-79), and high CVH (80-100). AF cases were obtained through linkage with registries. A Cox proportional hazards model adjusted for age, sex, education level, heart failure, coronary heart disease, and alcohol consumption, was used to assess the association between LE8 and AF. Results The mean age of participants was 49 years ± 12 years and 75% of participants were female. During a median follow-up of 15.3 years (interquartile range: 14.1 – 26.5 years), 833 AF cases (2.3%) were identified. Compared to the participants with a high CVH score (19.5%), participants with a low CVH score (5%) had a 2 times higher hazard for incident AF (hazard ratio (HR) 1.99 [95% confidence interval (95%CI) 1.49 – 2.65]). Furthermore, a decrease in the number of ideal components was associated with a higher risk for incident AF (HR 1.11 [95%CI 1.05 – 1.18]). Conclusions The results show that a worse CVH, indicated by a lower LE8 score, is associated with an increased risk for incident AF. Preventing AF could potentially be achieved by implementing the LE8 score in clinical practice. Especially since LE8 is a tool that is easy to interpret and can be applied by healthcare providers to encourage patients to make improvements in the risk factors for AF.

Association between cardiometabolic index and hepatic steatosis and liver fibrosis: a population-based study.

The cardiometabolic index (CMI) is a new type of obesity index that is based on a combination of lipid levels and abdominal obesity indicators. It is closely correlated with the occurrence of diabetes mellitus, atherosclerosis, hypertension, and other diseases, thus playing an important role in the screening of metabolic diseases. This is coupled with hepatic steatosis and fibrosis which are characterized by excessive liver fat deposition. The aim of this study was to investigate the possible association between CMI and hepatic steatosis and liver fibrosis. A cross-sectional investigation was conducted using the 2017-2020 National Health and Nutrition Examination Survey (NHANES) dataset to probe the relationship between CMI and hepatic steatosis and liver fibrosis, while multiple linear regression models were used to test the linear association between CMI and controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). Smooth-fit curves and threshold effects analysis were used to describe the nonlinear relationships. Subgroup analyses were performed according to gender, age, body mass index (BMI), hypertension, diabetes, cardiovascular disease, and smoking status. A total of 3084 adults aged 18-80 years were included in this analysis, and after controlling for a variety of variables, there was a significant positive correlation between CMI and CAP [20.38 (16.27,24.49)]. When subgroups were analyzed, this positive correlation was found to be stronger in the female population than in the male (P for interaction = 0.0303). Furthermore, the association between CMI and CAP was nonlinear. Using multiple regression analysis, it was shown that the linear relationship between CMI and liver fibrosis was not significant [-0.09 (-0.47,0.29)]. The findings suggest that elevated CMI levels are associated with hepatic steatosis, but that CMI is not linked to liver fibrosis. Larger prospective investigations are needed to confirm our findings.

Screening for elder mistreatment in a Swiss emergency department: a prospective cohort study.

The mistreatment of older adults is a global and complex problem with varying prevalence. As there are no data on the prevalence of elder mistreatment in European emergency department populations, we aimed to translate and culturally adapt the Emergency Department Senior Abuse Identification (ED Senior AID) tool for German use, assess the positive screen rate for elder mistreatment with the German version, and compare characteristics of patients who screened positive and negative. To assess the prevalence of elder mistreatment, we created a German version of the ED Senior AID tool. This tool identifies intentional or negligent actions by a caregiver or trusted person that cause harm or risk to an older adult. Then, the German ED Senior AID tool was applied to all consecutively presenting patients aged ≥65 years at our academic emergency department in the Northwest of Switzerland from 25 April to 30 May 2022. Usability was defined as the percentage of patients with completed assessments using the German ED Senior AID tool. We included 1010 patients aged ≥65 years, of whom 29 (2.9%) screened positive with the ED Senior AID tool. The patients who screened positive were older, more severely cognitively impaired, hospitalised more frequently, and presented with higher frailty scores than those who screened negative. Mortality up to 100 days after presentation was comparable in all patients (p = 0.861), regardless of their screening result. The tool showed good usability, with 73% of assessments completed. This is the first prospective investigation on the prevalence of elder mistreatment in a European emergency department setting. Overall, 2.9% of patients screened positive using a validated screening tool translated into German. This study was registered with the National Institute of Health on ClinicalTrials.gov with the registration number NCT05400707.

L-shaped association of systemic immune-inflammation index (SII) with serum soluble α-Klotho in the prospective cohort study from the NHANES database

The systemic immune-inflammation index (SII), an integrated and ground-breaking inflammatory measure, has been widely used in various fields. We aimed to assess the association between the systemic immune-inflammation index (SII) and α-Klotho (a new anti-aging biomarker). In this cross-sectional investigation, people with complete information on SII and α-Klotho from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2016 were the study's subject population. SII was calculated by platelet count × neutrophil count/lymphocyte count. The association between SII and α-Klotho was investigated using multivariable linear regression and a generalized additive model. In order to explore the non-linear connection, we employed smoothed curve fitting. Subgroup analysis were also performed. A total of 13,701 participants with an average age of 57.73 ± 10.86 years were enrolled, of whom 51.53% were female. After fully adjustment, SII was negatively associated with serum soluble α-Klotho [β(95% CI) = − 0.07 (− 0.08, − 0.05)]. Furthermore, we found L-shaped association between SII and klotho protein level, with the inflection point at 255 pg/ml. Subgroup analysis and interaction test revealed that there was no discernible dependence on gender, age, race, smoking, alcohol, diabetes and hypertension (all p for interaction > 0.05). SII level was negatively associated with serum klotho protein concentration in American adults. To verify our findings, more large-scale prospective investigations are still required.

Identification of potential novel N6-methyladenosine effector-related lncRNA biomarkers for serous ovarian carcinoma: a machine learning-based exploration in the framework of 3P medicine.

Serous ovarian carcinoma (SOC) is considered the most lethal gynecological malignancy. The current lack of reliable prognostic biomarkers for SOC reduces the efficacy of predictive, preventive, and personalized medicine (PPPM/3PM) in patients with SOC, leading to unsatisfactory therapeutic outcomes. N6-methyladenosine (m6A) modification-associated long noncoding RNAs (lncRNAs) are effective predictors of SOC. In this study, an effective risk prediction model for SOC was constructed based on m6A modification-associated lncRNAs. Transcriptomic data and clinical information of patients with SOC were downloaded from The Cancer Genome Atlas. Candidate lncRNAs were identified using univariate and multivariate and least absolute shrinkage and selection operator-penalized Cox regression analyses. The molecular mechanisms of m6A effector-related lncRNAs were explored via Gene Ontology, pathway analysis, gene set enrichment analysis, and gene set variation analysis (GSVA). The extent of immune cell infiltration was assessed using various algorithms, including CIBERSORT, Microenvironment Cell Populations counter, xCell, European Prospective Investigation into Cancer and Nutrition, and GSVA. The calcPhenotype algorithm was used to predict responses to the drugs commonly used in ovarian carcinoma therapy. In vitro experiments, such as migration and invasion Transwell assays, wound healing assays, and dot blot assays, were conducted to elucidate the functional roles of candidate lncRNAs. Six m6A effector-related lncRNAs that were markedly associated with prognosis were used to establish an m6A effector-related lncRNA risk model (m6A-LRM) for SOC. Immune microenvironment analysis suggested that the high-risk group exhibited a proinflammatory state and displayed increased sensitivity to immunotherapy. A nomogram was constructed with the m6A effector-related lncRNAs to assess the prognostic value of the model. Sixteen drugs potentially targeting m6A effector-related lncRNAs were identified. Furthermore, we developed an online web application for clinicians and researchers (https://leley.shinyapps.io/OC_m6A_lnc/). Overexpression of the lncRNA RP11-508M8.1 promoted SOC cell migration and invasion. METTL3 is an upstream regulator of RP11-508M8.1. The preliminary regulatory axis METTL3/m6A/RP11-508M8.1/hsa-miR-1270/ARSD underlying SOC was identified via a combination of in vitro and bioinformatic analyses. In this study, we propose an innovative prognostic risk model and provide novel insights into the mechanism underlying the role of m6A-related lncRNAs in SOC. Incorporating the m6A-LRM into PPPM may help identify high-risk patients and personalize treatment as early as possible.

Circulating free insulin-like growth factor-I and prostate cancer: a case-control study nested in the European prospective investigation into cancer and nutrition

BackgroundCirculating total insulin-like growth factor-I (IGF-I) is an established risk factor for prostate cancer. However, only a small proportion of circulating IGF-I is free or readily dissociable from IGF-binding proteins (its bioavailable form), and few studies have investigated the association of circulating free IGF-I with prostate cancer risk.MethodsWe analyzed data from 767 prostate cancer cases and 767 matched controls nested within the European Prospective Investigation into Cancer and Nutrition cohort, with an average of 14-years (interquartile range = 2.9) follow-up. Matching variables were study center, length of follow-up, age, and time of day and fasting duration at blood collection. Circulating free IGF-I concentration was measured in serum samples collected at recruitment visit (mean age 55 years old; standard deviation = 7.1) using an enzyme-linked immunosorbent assay (ELISA). Conditional logistic regressions were performed to examine the associations of free IGF-I with risk of prostate cancer overall and subdivided by time to diagnosis (≤ 14 and > 14 years), and tumor characteristics.ResultsCirculating free IGF-I concentrations (in fourths and as a continuous variable) were not associated with prostate cancer risk overall (odds ratio [OR] = 1.00 per 0.1 nmol/L increment, 95% CI: 0.99, 1.02) or by time to diagnosis, or with prostate cancer subtypes, including tumor stage and histological grade.ConclusionsEstimated circulating free IGF-I was not associated with prostate cancer risk. Further research may consider other assay methods that estimate bioavailable IGF-I to provide more insight into the well-substantiated association between circulating total IGF-I and subsequent prostate cancer risk.

Usage of Meropenem Continuous Infusion for Treatment of Infectious Complications in Orthopedic Elderly Patients with Anemia: A Case Series.

Background and Objectives: The prolonged infusion of meropenem is recommended by guidelines for the treatment of sepsis. However, studies provide controversial data on the advantages of prolonged infusions over intermittent ones. In our opinion, this can be related to age, which possibly distorts the final data, as older people have age-related characteristics. In our study, we analyzed the ventilatory status, laboratory tests and vital signs of the patient and carried out microbiological cultures. Materials and Methods: This was a prospective single-center case series investigation conducted from June 2022 to June 2023. The objective of this study was to evaluate the effectiveness of continuous infusion in elderly patients with severe infectious complications after orthopedic interventions. The primary endpoints were 28-day survival and the emergence of new multidrug-resistant strains. Secondary endpoints were long-term mortality and length of stay in the ICU. Results: Three patients (median age 65, 100% female) received a continuous infusion of meropenem. Two patients were alive at hospital discharge, and one patient died on the 105th day of hospitalization. Multi-resistant bacteria were observed in one patient. Conclusions: The use of a continuous meropenem infusion in the complex treatment of purulent-septic complications in elderly patients with periprosthetic infection and anemia probably led to clinical improvement in these case reports. However, the emergence of new pan-resistant strains and overall mortality using this infusion technique remains unclear. Further, high-quality RCTs for the elderly are needed.